Lyme disease (LD) and human granulocytic anaplasmosis (HGA), are significant public health threats. LD is caused by Borrelia burgdorferi, B. garinii, B. bavariensis, and B. afzelii. HGA is caused by Anaplasma phagocytophilum (Ap). The CDC estimates there are between 300-600,000 LD cases per year in the US with similar numbers in Europe. The number of cases of HGA is less clear but since being designated as a reportable disease in 2009, case numbers are steadily increasing. In 2010, active surveillance in endemic areas revealed an incidence rate of HGA of >50 cases per 100,000 population (a number considered to be a significant underestimate). Preventive strategies for tick borne diseases are ineffective. With the expansion of the endemic regions for LD and HGA, better recognition of their true incidence, the severity of these diseases, and the potential complications associated with co-infection, a vaccine that protects against multiple tick borne pathogens is needed. In this study we will develop a novel chimeric linear epitope based vaccine (chimeritope) for LD and HGA. Proof of principle for chimeritope vaccines has been demonstrated by the successful development of a highly efficacious canine LD vaccine. The same novel conceptual approach that was applied in developing the canine vaccine will be employed to construct a human vaccine for both LD and HGA. The chimeric vaccinogen will consist of defined linear epitopes of the OspA, B and C proteins of the Lyme disease spirochetes and defined domains of Ap proteins OmpA, Asp14 and AipA. The polyvalent nature of the construct will provide protection against diverse strains of the multiple species of Borrelia that cause LD and the causative agent of HGA. The resulting vaccine will offer a new preventive strategy for these significant public health threats. The proposed work is timely, highly significant and addresses an NIH priority area. This study will have broad overall impact as the knowledge gained can be applied in the design of other epitope based multi-valent, multi-disease vaccines.